Elevated glucose metabolism is a prominent characteristic of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA). However, the efficacy of inhibiting a single target of glucose metabolism in FLS using small molecular inhibitors is limited for RA treatment. Herein, the synergistic inhibition of FLS' survival, proliferation, and activation by combining two glucose metabolism inhibitors, diclofenac (DC) and lonidamine (LND) was first verified. Subsequently, DC and LND were individually conjugated to cystamine-modified hyaluronic acid (HA) to prepare two polymer-prodrug conjugates. A HAP-1 peptide-modified dual polymer-prodrug conjugates-assembled nanoparticles system (^HAP-1NP_DC+LND) was further tailored in the optimal synergistic ratio for targeted and synergistic metabolic modulation of FLS to alleviate RA symptoms. Upon targeted uptake by FLS in inflamed joints, ^HAP-1NP_DC+LND released DC and LND within the intracellular reductive microenvironment, where DC hinders glucose uptake and LND suppresses glycolytic enzymes to eliminate FLS synergistically. Additionally, the secretion of lactic acid and pro-inflammatory factors from FLS were reduced, thereby disrupting the crosstalk between FLS and pro-inflammatory macrophages. Finally, ^HAP-1NP_DC+LND demonstrated promising efficacy in a mouse model of collagen-induced arthritis (CIA). Overall, this research provides valuable insights into novel therapeutic strategies for the safe and effective of treatment RA through targeted and synergistic metabolic modulation of FLS.

Objective To investigate the clinical advantages and safety of an acupoint auto-positioning moxibustion robot combined with massage techniques in the treatment of lumbar disc herniation.Methods Totally 114 patients with lumbar disc herniation treated between June 2021 and December 2023 at Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,the Outpatient Department of Rehabilitation Medicine,Changhai Hospital and Shanghai Third Rehabilitation Hospital were divided into control group and experimental group with random number table method,with 57 cases in each group.The control group received conventional moxibustion combined with massage techniques,while the experimental group was treated using an acupoint auto-positioning moxibustion robot combined with massage techniques.Both groups underwent treatment once every three days,totaling 10 sessions over one month.Clinical efficacy was observed between the two groups by comparing pre-treatment and post-treatment(after 3,6 and 10 sessions)scores on the visual analogue scale(VAS)for pain,the Japanese Orthopaedic Association(JOA)lower back pain score,and lumbar range of motion(LROM).Adverse reactions during the intervention were recorded.Satisfaction with the moxibustion robot in the experimental group was assessed using a Likert scale.Additionally,20 healthy subjects were recruited to evaluate the accuracy of the robot's acupoint auto-positioning function.Results The overall effective rate was 91.23%(52/57)in the experimental group and 94.74%(54/57)in the control group,without statistical significance between the two groups(P>0.05).Compared to pre-treatment,both groups showed significant improvements in VAS scores,JOA scores and LROM across all measured directions after 3,6,and 10 treatment sessions(P<0.001).In the Likert scale assessment,86.96%of subjects agreed that the device was convenient to use,87.72%agreed that the device was safer than conventional moxibustion therapy,and 94.74%were willing to recommend the device to other patients.The accuracy evaluation of the acupoint auto-positioning moxibustion robot demonstrated that the average deviation between robot-positioned acupoints and standard acupoints was(1.68±0.46)mm,achieving a positioning accuracy rate exceeding 95%.No adverse reactions were reported during the intervention.Conclusion The combination of an acupoint auto-positioning moxibustion robot with massage techniques is as effective as conventional moxibustion combined with massage techniques in improving clinical symptoms,alleviating pains,enhancing lumbar function and increasing lumbar mobility in patients with lumbar disc herniation.Participants have exhibited a high willingness to use the device,and the robot achieved a high accuracy rate in acupoint positioning.

Objective:To explore the effect of exercise on the memory of rats modeling vascular cognitive impairment (VCI) and also its effects on the hippocampal Sema3G/neuropilin-2 (Nrp2)/PlexinA4 signaling pathway.Methods:Eighteen male Sprague-Dawley rats were randomly divided into a sham-operated group, a model group, and an exercise group, each of 6. The model and exercise groups underwent VCI modeling via bilateral common carotid artery occlusion, while the sham-operated group received the same surgical procedure without vessel ligation or transection. Beginning forty-eight hours after the surgery, the exercise group carried out daily 30-minute treadmill training sessions, 5 days a week, for a total of 4 weeks, while the other two groups were placed on the same treadmill with it not in operation. After the intervention, cognitive functioning was assessed using the novel object recognition (NOR) test and a Y-maze test. Western blotting was employed to evaluate the expression of Sema3G, Nrp2, PlexinA4, and Rac1 in the hippocampus. Immunofluorescence staining was used to observe the distribution of Nrp2 and PlexinA4 in the hippocampus.Results:Compared with the model group, the exercise group exhibited significantly higher NOR indices during both the short-term and long-term memory testing phases after the intervention. Those rats also tended to have significantly longer total exploration times in the novel arm of the Y-maze test. The western blotting revealed that the expression levels of Sema3G, PlexinA4, and Rac1 in the hippocampus were significantly higher in the exercise group compared to the model group, on average. Immunofluorescence showed significantly increased PlexinA4 fluorescence intensity in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus, and significantly elevated Nrp2 fluorescence intensity in the CA3 region in the exercise group compared to the model group. The Pearson correlation coefficients for Nrp2/PlexinA4 co-localization in the CA1, CA3 and DG regions were significantly higher in the exercise group than in the model group.Conclusions:Exercise training significantly improves memory function in rats with VCI, and this effect may be associated with activation of the hippocampal Sema3G/Nrp2/PlexinA4 signaling pathway.

Objective To investigate the distribution patterns of TCM syndrome elements and syndrome types in Klebsiella pneumoniae pneumonia.Methods The study adopted a retrospective research method to collect the basic demographic data,pathogenic characteristics,TCM syndrome patterns,and four diagnostic examination information(including tongue and pulse manifestations)of hospitalized patients with Klebsiella pneumoniae pneumonia at Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,from September 2022 to June 2024.Based on clustering analysis and factor analysis,the study explored the characteristics of TCM syndrome elements and the distribution patterns of TCM syndromes in Klebsiella pneumoniae pneumonia.Results A total of 365 patients(236 males,129 females)aged 23-100 years were included.Statistical analysis identified 33 core syndrome items,with cough being the most frequent(66.0%),followed by viscous phlegm(42.2%);the most common tongue characteristics were red tongue(50.4%)and greasy coating(45.8%),with slippery pulse being predominant(54.0%).Clustering analysis revealed four syndrome types:lung-kidney yin deficiency,phlegm-dampness with qi deficiency,yang deficiency with water overflow,and phlegm-heat obstructing the lung.Phlegm-heat obstructing the lung was the most prevalent(38.1%),followed by yang deficiency with water overflow(22.5%)and lung-kidney yin deficiency(22.2%).Factor analysis identified four common factors encompassing 21 variables,with a cumulative variance contribution rate of 74.888%.The results of syndrome elements were divided into phlegm,heat,qi stagnation,water retention,dampness,yang deficiency,yin deficiency,qi deficiency,and lung,kidney,heart,spleen based on pathological syndrome elements and pathological location syndrome elements.Conclusion Klebsiella pneumoniae pneumonia primarily affects the lungs,kidneys,heart,and spleen,with the lungs being the key organ.The most common TCM syndrome types are phlegm-heat obstructing the lung,lung-kidney yin deficiency,yang deficiency with water overflow,and phlegm-dampness with qi deficiency,among which phlegm-heat obstructing the lung is the most prevalent.

Objective To study the expression of N6-methyladenosine(m6A)methyltransferase-like protein 16(METTL16),Ankyrin repeat and SOCS box containing protein 4(ASB13)in elderly breast cancer tissues and their relationship with clinicopathological features and prognosis.Methods 124 elderly patients with breast cancer diagnosed and treated in the Zibo 148 Hospital from January 2019 to January 2021 were selected.Immunohistochemistry(IHC)was used to detect the expression of METTL16 and ASB13 proteins in tissues.Real time fluorescence quantitative PCR(RT-qPCR)was used to detect the expression of METTL16 mRNA and ASB13 mRNA in tissues.Pearson correlation was used for correlation analysis.Survival analysis used Kaplan-Meier curves and Log Rank tests to compare the prognostic differences among patients with different METTL16 and ASB13 expression levels.COX regression analysis was used to analyze the prognostic factors of elderly patients with breast cancer.Results The positive rate of METTL16 in cancer tissue(70.97%)was higher than that in adjacent tissues(8.06%),while the positive rate of ASB13(22.58%)was lower than that in adjacent tissues(72.58%),the differences were statistically significant(χ2=102.642,62.146,all P<0.001).METTL16 mRNA,Snail mRNA and N-cadherin(N-cd)mRNA were higher in cancer tissues than in adjacent tissues,while ASB13 mRNA was lower in adjacent tissues,the differences were statistically significant(t=40.498～48.624,all P<0.001).METTL16 mRNA was positively correlated with Snail mRNA and N-cd mRNA in cancer tissue(r=0.712,0.669,all P<0.001),while ASB13 mRNA was negatively correlated with Snail mRNA and N-cd mRNA(r=-0.734,-0.759,all P<0.001).Compared with TNM stage Ⅰ-Ⅱ and patients with high to medium differentiation,patients with TNM stage Ⅲ and low differentiation had higher positive rate of METTL16 in cancer tissue and lower positive rate of ASB13,the differences were statistically significant(χ2=5.340～10.370,all P<0.05).The 3-year progression free survival rate(73.86%)of the METTL16 positive group was lower than that of the METTL16 negative group(88.89%),the 3-year progression free survival rate(92.86%)of the ASB13 positive group was higher than that of the ASB13 negative group(73.96%),and the differences were statistically significant(Log Rank χ2=4.483,4.882,all P<0.005).METTL16 positive,TNM stage Ⅲ,poor differentiation were risk factors affecting the prognosis of elderly breast cancer,and ASB13 positive was protective factors(Wald χ2=5.056～9.267,all P<0.001).Conclusion METTL16 expression is up-regulated and ASB13 expression is down-regulated in elderly breast cancer,both of which are related to the expression of invasion and metastasis genes,and are new prognostic markers for elderly breast cancer.

Objective To analyze the current status and emerging technology trends in domestic medical drainage tube patents,so as to explore possible factors for low patent conversion rates.Methods Patents associated with"drainage tube","medical drainage tube","surgical drainage tube"and related terms were retrieved from the National Intellectual Property Administration Database and the Innojoy Patent Search Engine,covering the period from 2010 to 2020.Screening and visual analysis were conducted using Excel and SPSS 27.0.Results A total of 2 895 relevant patents were identified,comprising 2 489 utility model patents,367 invention patents and 39 design patents.The number of patent applications demonstrated a year-on-year growth trend,with a higher concentration in eastern coastal regions and provinces housing numerous top-tier hospitals and medical institutions.Approximately 49.26％of the patents filed by individuals were affiliated with hospitals,universities,or enterprises.Innovation hotspots included the design,functionality,performance,and safety aspects of drainage tubes and probes.Of the patents,72.61％were invalid,and 61.73％had a survival period of three years or less.Only 5.15％were commercially utilized through transfers,pledges,or licensing.Conclusion Domestic patent applications for medical drainage tubes have seen rapid growth,with a focus on enhancing tube structures such as sleeves,balloons,drainage holes,and threaded designs.However,the unsatisfactory situation of patent conversion and operation have been mainly limited by factors such as weak core technology of patents,insufficient awareness of achievements conversion,poor operation of patent conversion mechanism,insufficient market promotion,and insufficient integration of industry,academia,and research.To address this issue,enhancing intellectual property protection,revitalizing valid patents,and expanding transformation channels would benefit patients and facilitate hospitals'high-quality development,injecting new vitality into the health industry.

Purpose This study aimed to investigate the expression,function,and molecular mechanisms of ZNF384 in esophageal squamous cell carcinoma(ESCC),as well as its role in tumor progression and chemoresistance.Methods The expression of ZNF384 in ESCC cell lines and tissues was assessed using RT-qPCR.Correlations with TNM stage,invasion depth,lymph node metastasis,and prognosis were evaluated.In vitro assays were performed to examine the effects of ZNF384 on ESCC cell proliferation,migration,invasion,and chemosensitivity.Dual-luciferase reporter assays were conducted to determine the interaction between ZNF384 and FZD3,and to assess the activation of the Wnt signaling pathway.Results ZNF384 expression was significantly upregulated in ESCC cell lines and tissues(P＜0.01).Elevated ZNF384 expression was associated with advanced TNM stage,greater invasion depth,lymph node metastasis,and poor prognosis(P＜0.05).Functional assays demonstrated that ZNF384 overexpression promo-ted ESCC cell proliferation,migration,and invasion(all P＜0.01),whereas ZNF384 knockdown inhibited these processes and enhanced chemosensitivity to cisplatin(all P＜0.01).Mechanistic studies showed that ZNF384 directly bound to the FZD3 promoter,upregulated FZD3 expression,and activated the Wnt signaling pathway(P＜0.05).Overexpression of FZD3 partially reversed the inhibitory effects of ZNF384 knockdown on cell malignancy and chemore-sistance(P＜0.05).Conclusion ZNF384 promotes ESCC progression and reduces chemosensitivity through activa-tion of the FZD3/Wnt signaling pathway,suggesting its potential as a therapeutic target in ESCC.

Objective To study the expression of N6-methyladenosine(m6A)methyltransferase-like protein 16(METTL16),Ankyrin repeat and SOCS box containing protein 4(ASB13)in elderly breast cancer tissues and their relationship with clinicopathological features and prognosis.Methods 124 elderly patients with breast cancer diagnosed and treated in the Zibo 148 Hospital from January 2019 to January 2021 were selected.Immunohistochemistry(IHC)was used to detect the expression of METTL16 and ASB13 proteins in tissues.Real time fluorescence quantitative PCR(RT-qPCR)was used to detect the expression of METTL16 mRNA and ASB13 mRNA in tissues.Pearson correlation was used for correlation analysis.Survival analysis used Kaplan-Meier curves and Log Rank tests to compare the prognostic differences among patients with different METTL16 and ASB13 expression levels.COX regression analysis was used to analyze the prognostic factors of elderly patients with breast cancer.Results The positive rate of METTL16 in cancer tissue(70.97%)was higher than that in adjacent tissues(8.06%),while the positive rate of ASB13(22.58%)was lower than that in adjacent tissues(72.58%),the differences were statistically significant(χ2=102.642,62.146,all P<0.001).METTL16 mRNA,Snail mRNA and N-cadherin(N-cd)mRNA were higher in cancer tissues than in adjacent tissues,while ASB13 mRNA was lower in adjacent tissues,the differences were statistically significant(t=40.498～48.624,all P<0.001).METTL16 mRNA was positively correlated with Snail mRNA and N-cd mRNA in cancer tissue(r=0.712,0.669,all P<0.001),while ASB13 mRNA was negatively correlated with Snail mRNA and N-cd mRNA(r=-0.734,-0.759,all P<0.001).Compared with TNM stage Ⅰ-Ⅱ and patients with high to medium differentiation,patients with TNM stage Ⅲ and low differentiation had higher positive rate of METTL16 in cancer tissue and lower positive rate of ASB13,the differences were statistically significant(χ2=5.340～10.370,all P<0.05).The 3-year progression free survival rate(73.86%)of the METTL16 positive group was lower than that of the METTL16 negative group(88.89%),the 3-year progression free survival rate(92.86%)of the ASB13 positive group was higher than that of the ASB13 negative group(73.96%),and the differences were statistically significant(Log Rank χ2=4.483,4.882,all P<0.005).METTL16 positive,TNM stage Ⅲ,poor differentiation were risk factors affecting the prognosis of elderly breast cancer,and ASB13 positive was protective factors(Wald χ2=5.056～9.267,all P<0.001).Conclusion METTL16 expression is up-regulated and ASB13 expression is down-regulated in elderly breast cancer,both of which are related to the expression of invasion and metastasis genes,and are new prognostic markers for elderly breast cancer.

Objective To investigate the distribution patterns of TCM syndrome elements and syndrome types in Klebsiella pneumoniae pneumonia.Methods The study adopted a retrospective research method to collect the basic demographic data,pathogenic characteristics,TCM syndrome patterns,and four diagnostic examination information(including tongue and pulse manifestations)of hospitalized patients with Klebsiella pneumoniae pneumonia at Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,from September 2022 to June 2024.Based on clustering analysis and factor analysis,the study explored the characteristics of TCM syndrome elements and the distribution patterns of TCM syndromes in Klebsiella pneumoniae pneumonia.Results A total of 365 patients(236 males,129 females)aged 23-100 years were included.Statistical analysis identified 33 core syndrome items,with cough being the most frequent(66.0%),followed by viscous phlegm(42.2%);the most common tongue characteristics were red tongue(50.4%)and greasy coating(45.8%),with slippery pulse being predominant(54.0%).Clustering analysis revealed four syndrome types:lung-kidney yin deficiency,phlegm-dampness with qi deficiency,yang deficiency with water overflow,and phlegm-heat obstructing the lung.Phlegm-heat obstructing the lung was the most prevalent(38.1%),followed by yang deficiency with water overflow(22.5%)and lung-kidney yin deficiency(22.2%).Factor analysis identified four common factors encompassing 21 variables,with a cumulative variance contribution rate of 74.888%.The results of syndrome elements were divided into phlegm,heat,qi stagnation,water retention,dampness,yang deficiency,yin deficiency,qi deficiency,and lung,kidney,heart,spleen based on pathological syndrome elements and pathological location syndrome elements.Conclusion Klebsiella pneumoniae pneumonia primarily affects the lungs,kidneys,heart,and spleen,with the lungs being the key organ.The most common TCM syndrome types are phlegm-heat obstructing the lung,lung-kidney yin deficiency,yang deficiency with water overflow,and phlegm-dampness with qi deficiency,among which phlegm-heat obstructing the lung is the most prevalent.

Objective To analyze the current status and emerging technology trends in domestic medical drainage tube patents,so as to explore possible factors for low patent conversion rates.Methods Patents associated with"drainage tube","medical drainage tube","surgical drainage tube"and related terms were retrieved from the National Intellectual Property Administration Database and the Innojoy Patent Search Engine,covering the period from 2010 to 2020.Screening and visual analysis were conducted using Excel and SPSS 27.0.Results A total of 2 895 relevant patents were identified,comprising 2 489 utility model patents,367 invention patents and 39 design patents.The number of patent applications demonstrated a year-on-year growth trend,with a higher concentration in eastern coastal regions and provinces housing numerous top-tier hospitals and medical institutions.Approximately 49.26％of the patents filed by individuals were affiliated with hospitals,universities,or enterprises.Innovation hotspots included the design,functionality,performance,and safety aspects of drainage tubes and probes.Of the patents,72.61％were invalid,and 61.73％had a survival period of three years or less.Only 5.15％were commercially utilized through transfers,pledges,or licensing.Conclusion Domestic patent applications for medical drainage tubes have seen rapid growth,with a focus on enhancing tube structures such as sleeves,balloons,drainage holes,and threaded designs.However,the unsatisfactory situation of patent conversion and operation have been mainly limited by factors such as weak core technology of patents,insufficient awareness of achievements conversion,poor operation of patent conversion mechanism,insufficient market promotion,and insufficient integration of industry,academia,and research.To address this issue,enhancing intellectual property protection,revitalizing valid patents,and expanding transformation channels would benefit patients and facilitate hospitals'high-quality development,injecting new vitality into the health industry.